Abstract: An object of the present invention is to provide an amino acid precursor which shows improvement in the properties (particularly water-solubility, stability in water, bitter taste etc.) of amino acid, and can be converted to amino acid in vivo etc. The present invention relates to a compound for an amino acid precursor, which is a compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof.

Abstract: The present invention provides random copolymers containing phosphorylcholine and one or more functional agents, and methods of preparing such random copolymers.

Abstract: A composition that is a human growth hormone receptor antagonist comprising human growth hormone receptor antagonist G120K, wherein at least one amino acid of human growth hormone receptor antagonist G120K has been mutated to cysteine; and a polytethylene glycol molecule (PEG) conjugated to each cysteine residue in the human growth hormone receptor antagonist G120K mutant.

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Abstract: The present invention relates generally to glycoconjugates comprising a saccharide covalently conjugated to a carrier protein through a spacer containing ((2-oxoethyl)thio)). In an aspect the invention provides oxo-eT linked glycoconjugates comprising a saccharide covalently conjugated to a carrier protein through a ((2-oxoethyl)thio) spacer having the formula (I): (I) wherein: A is a group (C?X)m wherein X is S or O and m is 0 or 1; B is a bond, O, or CH2; and when m is 0, B can also be (C?O); R is a C2-C16 alkylene, C2-C16 heteroakylene, NH—C(?O)—C2-C16 alkylene, or NH—C(?O)—C2-C16 heteroakylene, wherein said alkylene and heteroalkylene are optionally substituted by 1, 2 or 3 groups independently selected from COOR? where R? is selected from H, methyl, ethyl or propyl. The invention further relates to immunogenic compositions comprising such glycoconjugates, and to methods for the preparation and use of such glycoconjugates and immunogenic compositions.

Abstract: The present invention relates to conjugates, in particular antibody-drug conjugates and immunotoxins, having the formula I: A-(L-D)p (I) or a pharmaceutically acceptable salts or solvates thereof, wherein: A is an antibody that selectively binds Endoglin; L is a linker; D is a drug comprising a cytolysin or a Nigrin-b A-chain; and p is 1 to 10, and to use of such conjugates in the therapeutic treatment of tumors. Methods of producing such conjugates and components for use in such methods are disclosed.

Abstract: The present invention provides multispecific antigen-binding molecules and uses thereof. The multispecific antigen-binding molecules comprise a first antigen-binding domain that specifically binds a target molecule, and a second antigen-binding domain that specifically binds an internalizing effector protein. The multispecific antigen-binding molecules of the present invention can, in some embodiments, be bispecific antibodies that are capable of binding both a target molecule and an internalizing effector protein. In certain embodiments of the invention, the simultaneous binding of the target molecule and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention results in the attenuation of the activity of the target molecule to a greater extent than the binding of the target molecule alone.

Abstract: The present invention relates to conjugates, in particular antibody-drug conjugates and immunotoxins, having the formula I: A-(L-D)p (I) or a pharmaceutically acceptable salts or solvates thereof, wherein: A is an antibody that selectively binds FAP; L is a linker; D is a drug comprising a cytolysin or a Nigrin-b A-chain; and p is 1 to 10, and to use of such conjugates in the therapeutic treatment of tumors. Methods of producing such conjugates and components for use in such methods are disclosed.

Abstract: The present invention relates to duocarmycin-containing antibody-drug conjugates (ADCs) for use in the treatment of human solid tumours expressing HER2, wherein the human solid tumour expressing HER2 is endometrial cancer, in particular uterine serous carcinoma (USC). In particular, the present invention relates to duocarmycin-containing ADCs for use in the treatment of endometrial cancer, notably USC, with HER2 IHC 2? or 1+ and HER2 FISH negative tumour tissue status.

Abstract: Disclosed herein are methods and compositions for treating cancer by increasing radiation-induced damage to cancer without increasing radiation-induced side effects by increasing secretory ASMase levels specifically in tumor endothelium, and inducing apoptosis of tumor endothelial cells by treating the tumor with radiation. ASMase levels are increased in tumor endothelium by administration of a recombinant DNA construct comprising a region coding for a functional ASMase linked to particular transcriptional regulatory sequences that confer tissue-specific expression of ASMase.

Abstract: Compositions and methods for treating macular degeneration are disclosed. The methods utilize gene delivery to human eyes of soluble Flt-1 receptors, as well fusion proteins including a soluble Flt-1 receptor.

Abstract: Disclosed are capsid-modified rAAV expression vectors, as well as infectious virions, compositions, and pharmaceutical formulations that include them. Also disclosed are methods of preparing and using novel capsid-protein-mutated rAAV vector constructs in a variety of diagnostic and therapeutic applications including, inter alia, as delivery agents for diagnosis, treatment, or amelioration of one or more diseases, disorders, or dysfunctions of the mammalian eye. Also disclosed are methods for intravitreal delivery of therapeutic gene constructs to retinal neuron cells, and specifically to ON bipolar cells, of the mammalian eye, as well as use of the disclosed compositions in the manufacture of medicaments for a variety of in vitro and/or in vivo applications including the treatment of retinitis pigmentosa, melanoma-associated retinopathy, and congenital stationary night blindness.

Abstract: Recombinant lentiviral vectors containing at least: a lentiviral backbone comprising essential lentiviral sequences for integration into a target cell genome; a nucleic acid encoding a CCR5 RNAi; and an expression control element that regulates expression of the nucleic acid encoding the CCR5 RNAi element, are provided by this invention. In an alternative aspect, the vector also contains polynucleotides encoding TRIM5 alpha and HIV TAR decoy sequences along with gene expression regulation elements such as promoters operatively linked to the polynucleotides. The vectors are combined with packaging plasmid and envelope plasmids and optionally conjugated to cell-specific targeting antibodies. Diagnostic and therapeutic methods for using the compositions are further provided herein.

Abstract: The present invention provides a unit dosage of Apadenoson, a pharmacological stress agent, and use of the same as a pharmacologic agent for myocardial perfusion imaging.

Abstract: Disclosed are compositions that comprise a cyclooxygenase-2-selective therapeutic and/or diagnostic agent having a therapeutic and/or diagnostic agent conjugated to a NSAID drug; and a ROS-responsive nanoparticle. Methods of making and using these compositions for drug encapsulation and delivery are also disclosed.

Abstract: The present disclosure discloses methods and compositions for A administering Cerenkov radiation-induced therapy (GRIT). In an aspect, the invention encompasses a composition comprising at least two radiation-sensitive molecules. In another aspect, the invention encompasses a composition comprising a radiation-sensitive molecule and a targeting agent. In still another aspect, the invention encompasses a method for administering Gerenkov radiation-induced therapy (GRIT) to a target tissue in a subject. The method comprises administering to the subject an effective amount of a composition B comprising at least one radiation-sensitive molecule and administering to the subject an amount of a Gerenkov radiation (GR)-emitting radionuclide effective to activate the radiation-sensitive molecule, thereby administering GRIT to the target tissue in the subject.

Abstract: Charged nanostructure being comprising gold nanoparticle which may bear on at least portion thereof a positively charged polymer wherein the positively charged polymer may bearon at least portion thereof a negatively charged polymer is disclosed. Uses thereof for diagnosis is also disclosed.

Abstract: A process for purifying a compound of formula 1, includes the following steps: a) adding an acid to an aqueous solution of the compound of formula 1, including salts and hydrates thereof so as to obtain a slurry having a pH?3; and b) filtering the slurry and at least one time washing the obtained precipitate with a liquid comprising water; and c) dissolving the precipitate obtained in step b) in water to obtain an aqueous solution; and d) filtering of the solution obtained in step c) over a nanofiltration membrane having a Molecular Weight Cut Off in the range from 150 to 500 and wherein optionally, between step c) and step d) the pH of the aqueous solution is adjusted to a pH value in the pH range as specified by the manufacturer of the nanofiltration membrane. A process for preparing a gadolinium complex of the purified compound of formula 1 is also disclosed. This gadolinium complex can be used for making a pharmaceutical composition as a contrast agent for magnetic resonance imaging.

Abstract: The present application discloses compositions and methods of use of 68Ga labeled molecules. Preferably, the 68Ga is attached to a peptide targetable construct and is used in a pretargeting technique with a bispecific antibody (bsAb). The bsAb comprises at least one binding site for a disease-associated antigen, such as a tumor-associated antigen, and at least one binding site for a hapten on the targetable construct. Exemplary haptens include In-DTPA and HSG. More preferably, the bsAb is administered about 24-30 hours before the targetable construct, and detection by PET imaging occurs about 1-2 hours after the targetable construct is administered. The methods and compositions are suitable for detection, diagnosis and/or imaging of various diseases, such as cancer or infectious disease.

Abstract: The present invention relates to systems and methods to facilitate replacement between runs of a kit or cassette from an automated radiosynthesis device located in a hot cell. The method and apparatus of the invention enable automated disconnection of the outlet line by sealing the tubing hermetically by means of heat and by cutting the tubing where it is sealed in such a way that there is no risk of environmental contamination with radioactive material. The invention enables disconnection of the outlet line without manual intervention before opening the shielded enclosure.

Abstract: The invention relates to a continuous sterilizing system comprising a sterilizing body into which a thermal fluid is introduced for sterilizing products, the products to be sterilized being arranged in containers that circulate inside the sterilizing body, said sterilizing body being divided into different sterilization zones by means of dividing walls, and each of said dividing walls having a through-opening that is substantially the same shape as a container, such that the containers close the through-openings of the dividing walls, rendering the sterilization zones thermally isolated from one another.

Abstract: A seal arrangement for sealing a space between a sterilization unit and adjacent walls in order to separate first and second rooms has a double seal gasket arrangement with a seal chamber there within. The seal chamber may be pressurized with a fluid and then the pressure within the seal chamber monitored by a pressure sensor. The double seal assembly provides an arrangement which can give an indication of the quality of the seal in order to detect any leakage and a more secure seal around the sterilization unit and as a result secure separation between a sterile or contaminated room and a general hospital area.

Abstract: A method and device for high-pressure, high-temperature steam sterilization of endoscopes includes pressure resistant fittings to attach a steam generator to the ports of an endoscope. The method and device allows for high-pressure, high-temperature steam to circulate throughout the endoscope, exposing various surfaces to steam for sterilization. The method and device also allows for high-pressure, high-temperature steam to circulate selectively through the channels of the endoscope, selectively sterilizing the channels and allowing for use of this method with current high-level disinfection methods. The method and device also allows for movement of the scope elevator channel during the sterilization process, allowing for steam to reach the crevices around the elevator and other moving parts of an endoscope.

Abstract: An instrument sterilization container may include a base, a lid, a retention mechanism extending out from a base floor of the base, a first support mechanism extending out from a lid top of the lid, and a second support mechanism extending out from the base floor. A reusable instrument handle may be disposed between the first support mechanism, the second support mechanism, the retention mechanism, and a portion of the base. The portion of the base and the retention mechanism may be configured to prevent an actuation structure of the reusable instrument handle from extending during a sterilization of the reusable instrument handle in a medical autoclave. The first support mechanism and the second support mechanism may be configured to prevent the actuation structure from expanding during a sterilization of the reusable instrument handle in a medical autoclave.

Abstract: Systems, devices, methods, and compositions are described for providing an actively controllable implant configured to, for example, monitor, treat, or prevent microbial growth or adherence to the implant.

Abstract: An automatic air freshener that operates for a period of time in excess of about 14 days, and that may optionally include a drain cleaner, mosquito repellant, or other beneficial fluid. Certain embodiments are adapted for disposal in a urinal, although a variety of other applications are contemplated. An air freshener may operate by: emanation of scent from a rubber or rubber-like material that carries a dispersed scented oil; gravity-induced drip from a bulk supply of scented fluid through a small orifice; osmotic transfer of scented fluid from a bulk supply; or gas-pump drive of scented fluid at controlled pressure. When present, the drain cleaner typically is carried by a container structured to permit a slow drip of drain cleaning fluid from a bulk fluid supply.

Abstract: A device for dispersing foul gaseous effluent emissions released diffusely by sources located close to the ground, in particular by wastewater treatment ponds (10, 11, 12), includes: at least two auxiliary air or gas injectors (5a1, 5b1; 5a2, 5b2; 5a3, 5b3) oriented upwards and installed in opposing zones on the periphery of each foul gaseous effluent source, such as to disperse the gaseous effluents; separate supply elements (8.1, 13a1,13b1; 8.2, 13a2, 13b2; 8.3, 13a3, 13b3) for the injectors; and wind-direction-sensitive control elements for ensuring that at least the injector(s) best located to disperse and/or lift the gaseous effluent plume are supplied.

Abstract: A high efficiency ultra-violet air purification system is disclosed. The system includes an apparatus for purifying air. The apparatus includes a chamber having a hollow interior and having an inlet and an outlet, the chamber having an inner reflective surface. The apparatus further includes an ultraviolet (UV) light source mounted within the hollow interior of the chamber between the inlet and the outlet. The apparatus further includes a honeycomb structure mounted to each of the inlet and the outlet of the UV chamber, the honeycomb structure having an array of hexagonal passages that are orthogonal to the inner reflective surface of the chamber, each hexagonal passage being at least partly coated with a UV catalyst and a UV light absorption coating.

Abstract: A method to regrow a protective layer over exposed/demineralized dentin that includes a step of identifying a subject having exposed/demineralized dentin. The demineralized dentin is contacted with a remineralization composition that includes an amelogenin and derived peptides, a chitosan, water, and a sufficient amount of a pH adjusting component such that the composition has a pH greater than about 6.0 such that dentinal tubules are occluded with apatite crystals and enamel is regrown on the dentinal tubules.

Abstract: The inventions provided herein relate to compositions, methods, delivery devices and kits for repairing or augmenting a tissue in a subject. The compositions described herein can be injectable such that they can be placed in a tissue to be treated with a minimally-invasive procedure (e.g., by injection). In some embodiments, the composition described herein comprises a compressed silk fibroin matrix, which can expand upon injection into the tissue and retain its original expanded volume within the tissue for a period of time. The compositions can be used as a filler to replace a tissue void, e.g., for tissue repair and/or augmentation, or as a scaffold to support tissue regeneration and/or reconstruction. In some embodiments, the compositions described herein can be used for soft tissue repair or augmentation.

Abstract: Provided is an implant configured to fit at or near a bone defect to promote bone growth, the implant comprising: a biodegradable polymer in an amount of about 0.1 wt % to about 20 wt % of the implant and an oxysterol in an amount of about 20 wt % to about 90 wt % of the implant. The implant has a high oxysterol load. Methods of making and use are further provided.

Abstract: Provided herein are bone grafts and methods of making and using the same, as well as products and kits that include such bone grafts. In particular, bone grafts are provided that include collagen Type I and one or more different types of mineral compositions having different dissolution properties and/or sizes, to enhance bone regeneration throughout the bone healing phase.

Abstract: Disclosed herein are methods of producing a cartilaginous implant by producing a polymer scaffold composition by electrospinning a polymer solution onto a collector in order to obtain polymer fibers; crosslinking the polymer fibers; and adding a plurality of cells to the polymer scaffold composition, wherein the plurality of cells comprises cartilaginous cells to form a cartilaginous implant.

Abstract: Disclosed are solid and frozen haemostatic materials and dressings consisting essentially of a fibrinogen component and a fibrinogen activator. Also disclosed are methods of treating internal wounded tissue in a mammal by applying one or more of these haemostatic materials and dressings, particularly for the treatment of injured tissue via endoscopic or minimally-invasive surgical techniques.

Abstract: An antimicrobial medical device that includes a substrate having a metal surface that is made from a metal or metal alloy that may include stainless steel, cobalt, and titanium. Disposed on the metal surface is a first antimicrobial oxide layer that includes an antimicrobial metal that may include silver, copper, and zinc, and combinations thereof. The atoms of antimicrobial metal in the first antimicrobial oxide layer are of a first concentration. The first antimicrobial oxide layer is positioned in a direction opposite that of the metal surface. The device further includes a second antimicrobial oxide layer that includes an antimicrobial metal that may be silver, copper, and zinc, and combinations thereof. The atoms of the antimicrobial metal present in the second antimicrobial oxide layer are of a second concentration. The first concentration and the second concentration are not equal. Methods for making the antimicrobial medical device are also disclosed.

Abstract: A method for producing an antimicrobial coating on a surface. The method includes mixing a parylene dimer and an antimicrobial agent to form a mixture, heating the mixture to sublimate the parylene dimer and suspend the antimicrobial agent within the sublimated parylene dimer, pyrolyzing the sublimated parylene dimer to form a parylene monomer while the antimicrobial agent is suspended within the parylene monomer, and condensing the parylene monomer and the antimicrobial agent together on the surface to polymerize the parylene monomer and form a coating containing a parylene polymer and the antimicrobial agent.

Abstract: The present invention relates to coatings with crystallized active agent(s) and related methods. In an embodiment, the invention includes a method for coating a medical device including selecting a solvent and a polymer, selecting a concentration of an active agent of at least a certain amount of saturation, forming a coating composition having the selected concentration of the active agent, and applying the coating composition to the medical device. In an embodiment, the invention includes an elution control coating disposed on a medical device, the elution control coating including a polymer, and an active agent, wherein the active agent is at least about 80% crystallized within one week of being disposed on the medical device.

Abstract: A system and method for determining location of a fluid leak at a drape of a reduced pressure delivery system being used on a tissue site of a patient may include applying a reduced pressure to the tissue site of the patient. The drape may be imaged to generate image data, and a determination of a location of a fluid leak of the drape may be made from the image data. As a result of the determination of the location of the fluid leak, the drape may be corrected. The imaging may be made in a non-visible spectrum. The non-visible spectrum may be in an IR spectrum or UV spectrum. In one embodiment, a fluid, such as compressed air, may be applied to the dressing via the interface between the drape and tissue of the patient to improve imaging in the non-visible spectrum.

Abstract: A fluid level sensor assembly for monitoring a fluid level in a fluid collection canister of a medical waste fluid collection system. The fluid level sensor assembly includes a fluid level sensor configured for monitoring the fluid level in the fluid collection canister and a fluid level sensor cover configured for preventing direct contact between the fluid level sensor and a fluid in the fluid collection canister. The fluid level sensor cover includes a polymeric cap and polymeric sheath extending from the cap. The elongate tubular sheath surrounds an elongate probe of the sensor with the cap positioned at a base of a sensor body of the sensor to prevent direct fluid contact with the elongate sensor probe and the sensor body.

Abstract: A system and method for performing tissue therapy may include applying a reduced pressure to a tissue site, sensing a fluid parameter being applied to the tissue site, generating a fluid sensor signal in response to sensing the fluid parameter, and altering the fluid sensor signal in response to sensing that the fluid parameter changes. A fluid leak location mode may be entered. In response to the fluid leak location mode being entered, a graphical user interface that provides for fluid leak location functionality may be displayed. In one embodiment, the fluid leak location mode may be automatically entered in response to the sensor signal crossing a threshold value. Additionally, an alarm signal may be generated in response to determining that the fluid sensor signal crosses the threshold value.

Abstract: A thorax drainage device for aspirating fluids from a pleural cavity of a patient using underpressure has a fluid collection container for collecting the aspirated fluids and a drainage tube for connecting the fluid collection container to the pleural cavity of the patient. The fluid collection container is connectable to a vacuum source, in order to generate an underpressure in the fluid collection container. The thorax drainage device has an adjustable mechanism for attenuating pressure differences during the respiration of the patient, this mechanism being adjustable independently of a suction capacity of the vacuum source. This device permits a gradual expansion of the lung without risk of injury and thus prepares the lung for the completion of the drainage.

Abstract: An in-joint pump and control device comprising a pump and an in-joint sensor. The pump is configured to convey fluid to a body joint surgical site. The pump has an algorithm associated therewith to make calculations and to assist in controlling the operation of the pump. The in-joint sensor is operatively associated with the pump by at least a communication member. The in-joint sensor comprises a sheath, an integration member attached to the sheath, a pressure sensor connected to the integration member, and a temperature sensor adjacent the sheath. The pressure sensor is adapted to provide pressure information to the pump via the communication member. The temperature sensor is also adapted to provide temperature information to the pump via the communication member.

Abstract: Embodiments disclosed herein are directed to negative pressure treatment systems and wound dressing systems, apparatuses, and methods that may be used for the treatment of wounds. In particular, some embodiments are directed to improved wound dressings comprising an obscuring layer that may hide fluid contained therein and a stabilizing structure that may aid in wound closure.

Abstract: A mechanical wound therapy (MWT) system includes a connection for a vacuum source, which is routed through an airtight covering to a porous material positioned over the wound. The porous material may be a tubing network interspaced by a netting material constructed of biologically inert or bioabsorbable material. Alternatively, the porous material may be a layered unified dressing in which layers of mesh, netting or thin perforated film are separated and fixedly attached to functional elements of the dressing (e.g., irrigation tubing) or spacers. The vacuum and irrigation systems may be completely separated. An airtight sealing layer or foldable adhesive sealing layer may seal the dressing and facilitate sealing the dressing to the wound margins. Additional modular devices such as a wound approximating system, positive pressure bladders and adjuvant therapy modules as well as enhanced monitoring technology can be added to synergistically increase the capabilities of each dressing.

Abstract: An apparatus for cleansing wounds, in which wound exudate is removed from a wound bed and selectively cleansed and returned to the wound. The cleansing means removes materials deleterious to wound healing, and the cleansed fluid, still containing materials that are beneficial in promoting wound healing, is returned to the wound bed. The associated wound dressing and cleansing means are conformable to the wound, and may have irrigant fluid circulated from a reservoir by a device for moving fluid through a flow path which passes through the dressing and a means for fluid cleansing and back to the dressing.

Abstract: An endovascular assembly for improving vessel compliance by reducing the blood pressure needed to eject a given volume of blood. The assembly comprises a first expandable container, a balloon for example, positioned in the vascular system. The first container has a variable volume in response to blood flow in the vessel, and is fixed to at least one expandable attachment member. When the attachment member is expanded inside of the vasculature, the attachment member is preferably fixed inside the vessel. The assembly further comprises a second container, preferably having a fixed volume that forms a closed fluid system when fluidly connected to the first container. The connection between the first and second container permits a change in volume in the first container to flow fluid into the second container. The second container can be placed in a different location inside of the patient, preferably outside of the vessel.

Abstract: Extracorporeal circuit devices that can be used for on-pump open-heart surgery to support surgical procedures such as coronary artery bypass grafting are described. In some embodiments, an oxygenator can include an integral pump. Such an integrated arrangement can advantageously provide an extracorporeal circuit with a lower overall volume than other conventional extracorporeal circuits.

Abstract: An extracorporeal blood processing system comprises a plastic molded compact manifold that supports a plurality of molded blood and dialysate fluidic pathways along with a plurality of relevant sensors, valves and pumps. A disposable dialyzer is connected to the molded manifold to complete the blood circuit of the system. The compact manifold is also disposable in one embodiment and can be detachably installed in the dialysis machine.

Abstract: Separation of a wash liquid from red blood cells is disclosed using a filter separation and pressure differential system. The filter may include a membrane filter.

Abstract: The object of the invention is to provide a blood separation device that can reduce the total time for drawing blood to obtain high-concentration platelet liquid, thereby reducing the binding time of the blood donor. The device includes a temporary storage bag (Y2) (also serves as a buffy coat bag) which is a whole blood bag for storing whole blood drawn from a blood donor. The controlling unit of the device controls the device to draw whole blood from the blood donor in parallel with at least either a circulation flow step or an acceleration step, thereby storing the drawn whole blood in the temporary storage bag (Y2).